Ethyl diethylphosphorylmethanesulfonate → N,beta,beta-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-(ethoxysulfonyl)-1-isopropylprop-2-enyl]-N1,3-dimethyl-L-valinamide

HRID 133816Notes

Reaction equation

HRID 133816 reaction equation
C(P([CH2:7][S:8]([O:11][CH2:12][CH3:13])(=[O:10])=[O:9])(CC)=O)C.C([Li])CCC.[CH:19]([CH:21]([N:25]([CH3:48])[C:26]([CH:28]([NH:33][C:34](=[O:47])[CH:35]([NH:45][CH3:46])[C:36]([CH3:44])([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:37])[C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:22]([CH3:24])[CH3:23])=O>C1COCC1>[CH3:46][NH:45][C@H:35]([C:34]([NH:33][C@H:28]([C:26]([N:25]([C@@H:21]([CH:22]([CH3:24])[CH3:23])/[CH:19]=[CH:7]/[S:8]([O:11][CH2:12][CH3:13])(=[O:9])=[O:10])[CH3:48])=[O:27])[C:29]([CH3:30])([CH3:31])[CH3:32])=[O:47])[C:36]([CH3:37])([CH3:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 18542441Ethyl diethylphosphorylmethanesulfonateHCID 72370856N-{1-[(1-Formyl-2-methyl-propyl)-methyl-carbamoyl]-2,2-dimethyl-propyl}-3-methyl-2-methylamino-3-phenyl-butyramideHCID 178418339Butyllithium

Product 1

HCID 11706341N,beta,beta-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-(ethoxysulfonyl)-1-isopropylprop-2-enyl]-N1,3-dimethyl-L-valinamideYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl diethylphosphorylmethanesulfonate (260 mg, 1.0 mmol) in anhydrous THF (3 mL) at −78° C. is added n-butyllithium (in hexanes, 0.44 mL, 1.1 mmol). After stirring for 20 min at −78° C., a solution of N-{1-[(1-Formyl-2-methyl-propyl)-methyl-carbamoyl]-2,2-dimethyl-propyl}-3-methyl-2-methylamino-3-phenyl-butyramide (1.0 mmol) in anhydrous THF (7 mL), which is freshly prepared as described in Reference Example 12, is added. The reaction mixture is stirred at −78° C. for additional 30 min, and then gradually warmed to room temperature. After 40 h, the reaction is quenched with water and extracted with CH2Cl2. The combined organic layers are washed with brine, dried (Na2SO4), filtered and concentrated. The residue is chromatographed on a silica gel column, eluting with 4:1 CH2Cl2/EtOAc to give 160 mg (31%) of the title compound as a yellow oil. HRMS (ESI) calcd for C27H45N3O5S [M+H] 524.3153, found 524.3157.

Workup

  1. additionis added
  2. stirringThe reaction mixture is stirred at −78° C. for additional 30 min
  3. temperaturegradually warmed to room temperature
  4. waitAfter 40 h
  5. customthe reaction is quenched with water
  6. extractionextracted with CH2Cl2
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is chromatographed on a silica gel column
  12. washeluting with 4:1 CH2Cl2/EtOAc

Sources & evidence

ORD record
ord-47b4b23c720e4b609e1b6ace70fe4170
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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